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Biomedical subjects

A Bustamante

Publications and source records attributed to A Bustamante.

At least 19 recordsLinked to original sources

Benefits of early biopsy on the outcome of kidney transplantation.

INTRODUCTION: Delayed graft function has been associated with worse long-term kidney allograft survival. Adequate diagnosis of the etiology of dysfunction is crucial, often requiring routine early biopsies. The aim of this article was to report the results and safety of early kidney allograft biopsies and how they influenced its management. METHOD: Between September 1994 and July 2004, 134 renal transplant recipients were prescribed cyclosporine (CsA; Neoral, Novartis, Chile), steroids, and a third agent (azathioprine in 92% of the graft recipients). Thirty-four patients (26%) had a kidney biopsy performed within the first week because of allograft dysfunction. RESULTS: The main diagnosis was acute tubular necrosis (ATN) in 22 patients (65%), whereas 6 (18%) were diagnosed with an acute rejection episode (ARE), allowing prompt initiation of therapy with reversal of rejection in 4 of them. Two patients (6%) showed signs of thrombotic microangiopathy (TMA) induced by CsA, which subsided following a switch from CsA to tacrolimus (Prograf Pharmainvesti, Chile). In 2 patients, the biopsy specimen showed signs of CsA nephrotoxicity that reverted following dose reduction. Finally, in 2 patients, the biopsy specimen showed chronic nephropathy of donor origin, which had not been previously recognized, resulting in graft loss. There was only one major complication related to the biopsy, intraperitoneal bleeding that required surgical treatment. CONCLUSIONS: Early allograft biopsy is safe and, in a significant number of cases (30%), it detects important allograft pathology (ARE, TMA, and drug toxicity), which when adequately and promptly treated may rescue the graft.

Acute Disease↗

Genetic diversity and differentiation of guanaco populations from Argentina inferred from microsatellite data.

Genotype data from 14 microsatellite markers were used to assess the genetic diversity and differentiation of four guanaco populations from Argentine Patagonia. These animals were recently captured in the wild and maintained in semi-captivity for fibre production. Considerable genetic diversity in these populations was suggested by the finding of a total of 162 alleles, an average mean number of alleles per locus ranging from 6.50 to 8.19, and H(e) values ranging from 0.66 to 0.74. Assessment of population differentiation showed moderate but significant values of F(ST)=0.071 (P=0.000) and R(ST)=0.083 (P=0.000). An amova test showed that the genetic variation among populations was 5.6% while within populations it was 94.4%. A number of 6.6 migrants per generation may support these results. Unambiguous individual assignment to original populations was obtained for the Pilcaniyeu, Las Heras and La Esperanza populations. The erroneous assignment of 18.75% Rio Mayo individuals to the Las Heras population can be explained by the low genetic differentiation found between these two populations. Thirty-nine of 56 loci per population combinations were in Hardy--Weinberg disequilibrium because of guanaco heterozygote deficiency, which may be explained by population subdivision. The high level of genetic diversity of the guanacos analysed here indicates that the Patagonian guanaco constitutes an important genetic resource for conservation or economic utilization programmes.

Analysis of Variance↗

Study of the activity of glutathione-peroxidase, glutathione-transferase, and glutathione-reductase in renal transplants.

The aim of this work was to study the temporare variation of oxidative stress in the plasma and erythrocytes (CR) of renal transplant patients We determined total glutathione (GST), as well as oxidized (GSSG) and reduced (GSH) fractions and the activity of glutathione peroxidase (G-px), glutathione reductase (G-red) and glutathione transferase (GSt). Determinations were performed 48 hours before transplant as well as 1 and 2 weeks after the renal transplant. The results showed a high "oxidative stress" rate, resulting from the equilibrium between the production of free radicals and the activity of antioxidants, the former being higher proportionally. Immediately after the transplant, there was an increase in oxidative stress, which resulted in an increased G-red, a marked decrease in plasma and in erythrocyte G-px (CR9 and an abrupt drop both in GST levels in plasma and in GSG (as well as in the [GSH]/[GSSG] relationship). Thereafter there was a significant improvement in the activity of antioxidant enzymes, but without normalization; the total glutathione levels and the activity of various enzymes approached the average values of the control group.

Erythrocytes↗

Invasive meningococcal disease in adolescents and young adults.

CONTEXT: Incidence of invasive meningococcal disease has increased recently in persons aged 15 through 24 years. OBJECTIVE: To characterize meningococcal infection in adolescents and young adults in Maryland during the 1990s. DESIGN AND SETTING: Population-based surveillance study for meningococcal disease from January 1, 1990, through December 31, 1999, in Maryland. PATIENTS: Maryland residents diagnosed as having invasive meningococcal disease. MAIN OUTCOME MEASURE: Invasive meningococcal infection. RESULTS: Of 295 total cases, 71 (24.1%) occurred among persons aged 15 through 24 years. Sixteen (22.5%) of these cases were fatal. The annual incidence rate increased from 0.9 to 2.1 cases per 100 000 among 15 through 24 year olds (P =.01). The proportion of all disease increased from 16.0% to 28.9% (P =.03). The incidence and proportion of cases subsequently decreased to 1.0 and 16.4% in 1998 through 1999, respectively. Infection in 15 through 24 year olds was more likely to be fatal than infection in those younger than age 15 years (22.5% vs 4.6%; P =.001). Infection in 15 through 24 year olds, compared with those aged 25 years or older, was more likely to be associated with male sex (66.2% vs 34.8%; P<.001) and serogroup C infection (46.9% vs 20.2%; P<.001), respectively. Infections were potentially preventable with the licensed meningococcal vaccine in 82.8% of 15 through 24 year olds, 68.1% of those younger than 15 years, and 76.8% of adults aged 25 years or older. CONCLUSIONS: Incidence of meningococcal infection in 15 through 24 year olds in Maryland increased and then declined during the 1990s. Infection in this age group was associated with an unusually high case-fatality ratio, and the vast majority of cases were potentially vaccine preventable.

Adolescent↗

Evaluation of a latex agglutination kit (Virogen Rotatest) for detection of bovine rotavirus in fecal samples.

The performance of the Virogen Rotatest latex agglutination test (LAT) was evaluated for detection of bovine rotavirus antigen. Sixty-three fecal samples from diarrheic calves were collected from November 1999 to May 2000 and screened by LAT, the Rotazyme II enzyme-linked immunosorbent assay (ELISA), and virus isolation (VI) followed by an anti-rotavirus fluorescent-antibody (FA) test to detect the presence of group A rotavirus antigen. Of the 63 samples screened by VI-FA, 33 (58%) tested positive for rotavirus antigen. When the results from the LAT were compared to those from VI-FA, the "gold standard" for detection of bovine rotavirus in fecal samples, the sensitivity and specificity were found to be 87.8 and 73.3%, respectively. Latex agglutination compared with ELISA (the reference method) showed 100% sensitivity and 96.3% specificity, and when ELISA was compared with VI, the sensitivity was 84.8% and the specificity was 73.3%. Latex agglutination is easy to perform in a short time and does not require expensive equipment or skilled personnel, and the reagents have long shelf lives. These factors make the LAT suitable and highly efficient for use in a clinical laboratory as a rapid screening test for bovine rotavirus.

Animals↗

Usefulness of a national registry of alpha-1-antitrypsin deficiency. The Spanish experience.

Severe alpha-1-antitrypsin (AAT) deficiency, phenotype Pi ZZ, is a rare condition with an estimated prevalence of 1/4500 individuals in Spain. Given this low prevalence, it seems useful to accumulate all the information derived from the care of these patients. In this context, the Spanish Registry of patients with AAT deficiency was founded in 1993; its main objectives were to establish guidelines adapted to our country for the treatment and management of AAT-deficient patients, offer expert support to physicians all over the country treating these patients, and provide technical support on the determination of Pi phenotyping and genotyping of individuals suspected of being AAT-deficient. From 1993 to January 1998 the number of enrollees increased from 48 to 223, of which 216 were Pi ZZ. Seventy-three per cent were male and only 31.5% were never smokers, mean age was 46 years (SD = 13 years) and mean FEV1 53% predicted (SD = 31%). 83% were index cases who, compared with non-index cases, were older (49 +/- 11 vs. 35 +/- 13 years, P < 0.001), more likely to have a smoking history (85% vs. 47%, P < 0.01) and displayed more severe impairment in pulmonary function (FEV1% = 40% +/- 19% vs. 96% +/- 23%, P < 0.001). Augmentation therapy was administered to 129 patients (58%). Treated patients had more severe impairment in pulmonary function than the untreated (FEV1% = 40% +/- 21% vs. 72% +/- 32%, P < 0.001) and were more likely to be index cases (81% vs. 43%, P < 0.001). Characteristics of the patients included are similar to those described for other Registries. The Registry has extended knowledge of the disease throughout the country and has established local guidelines for treatment and follow-up. It may be a valid database for future co-operation in international initiatives.

Adult↗

Novel phosphonium salts display in vitro and in vivo cytotoxic activity against human ovarian cancer cell lines.

Phosphonium salts are part of a class of lipophilic cationic molecules that accumulate preferentially in mitochondria and inhibit the growth of human and rodent carcinoma cells in vitro and in animal models. The delocalized cations tested previously such as dequalinium have exhibited considerable cross resistance against multiple drug-resistant cells expressing gp 170. In order to overcome this cross resistance, we have developed two novel phosphonium salts which contain haloalkyl moieties with potential protein alkylating capabilities. 3-Chloropropyltris(4-dimethylaminophenyl)phosphonium chloride (APPCL) and 3-iodopropyltris(4-dimethylaminophenyl)phosphonium iodide (APPI) are more lipophilic than other phosphonium salts described to date. By comparing the 50% inhibitory concentration (IC50) values for the A2780 human ovarian carcinoma parental line to a multiple drug-resistant variant (A2780-DR), the degree of cross resistance (IC50 for A2780-DR/IC50 for A2780 Parental) were found to be 494 for doxorubicin, but only 2.7 for APPCL. Similarly, the degree of cross resistance using a cisplatin-resistant variant (IC50 for A2780-CR/IC50 for A2780 Parental) was 30 for cisplatin, but only 2.2 for APPCL. APPCL is also active in vitro against UCI 101 (IC50 = 80 nM), an ovarian carcinoma line isolated from a patient who had failed chemotherapy with taxol, doxorubicin, and high-dose cisplatin. The cytotoxicity of APPI was comparable to that of APPCL with an IC50 ranging from 16.7 to 83.0 nM for a panel of seven cell lines. When administered intraperitoneally at a total dose of 46 mg/kg over 15 days, APPCL increased the median lifespan of nude mice bearing UCI 101, from a control value of 48.0 to 92.5 days (P < 0.0061). The median survival of the APPI-treated mice was 55 days. A total of 37.5% of the APPCL-treated group and 12.5% of the APPI-treated group were long-term survivors: sacrifice of these mice on Day 180 and subsequent histology showed no evidence of disease. Exposure to APPCL and APPI caused mitochondrial damage to UCI 101 cells at sublethal doses in vitro, as shown by morphological damage observed with transmission electron microscopy. APPCL appears to decrease the uptake of rhodamine 123 by mitochondria, suggesting that mitochondria may be significant targets or initial reservoirs for this agent. In conclusion, APPI and APPCL show promising anticancer activity against a variety of human ovarian carcinoma cell lines warranting further investigation.

Animals↗

Suramin sodium: pronounced effects on methotrexate transport and anti-folate activity in cultured tumor cells.

Suramin is an experimental anti-neoplastic agent which has shown promising activity against prostatic carcinoma and lymphoma in clinical trials. To elucidate its mechanism of action, suramin was examined for an effect on the transport of folate compounds by tumor cells. Influx of the anti-folate methotrexate via the reduced-folate carrier system of CCRF-CEM cells was found to be highly sensitive to inhibition by suramin but not to various other arylsulfonic acids. Inhibition by suramin was competitive, and the inhibition constant Ki was 1.3 microM, a value 3-fold lower than the Kt for half-maximal influx of methotrexate. Folate binding to the membrane-associated folate-binding protein of KB cells was not affected by suramin. Growth studies revealed that the response of human CCRF-CEM, KB, PC-3 and MCF-7 cells to methotrexate was antagonized from 6- to 17-fold by pharmacological levels (10-200 microM) of suramin. Conversely, growth inhibition was additive or synergistic when suramin was combined with metoprine, a lipophilic anti-folate which enters cells by diffusion. Synergism was observed between metoprine and suramin in CCRF-CEM cells, which take up folate exclusively through the reduced-folate carrier (inhibitable by suramin), whereas additivity was observed for KB cells, which rely largely on the folate-binding protein (unaffected by suramin) for folate import. Our results indicate that inhibition of cellular transport of folate compounds may explain part of the anti-neoplastic effects of suramin on tumor cells.

Antineoplastic Agents↗

Mechanism of inhibition of FaDu hypopharyngeal carcinoma cell growth by tetraphenylphosphonium chloride.

Cationic phosphonium salts are interesting because they inhibit the proliferation of carcinoma cells more than untransformed epithelial cells in vitro. This differential anti-proliferative effect has been used to identify phosphonium salts and other lipophilic cations that later demonstrated effects in animals. Using 6 carcinoma-derived and 2 untransformed epithelial cell lines, tetraphenylphosphonium chloride (TPP) and other cationic aryl phosphonium salts (CAPS) demonstrated a growth inhibition pattern similar to that of cation rhodamine 123, suggesting that CAPS may inhibit mitochondrial function. We tested this hypothesis for the effect of phosphonium salt TPP on FaDu human hypopharyngeal carcinoma cells. TPP inhibited the proliferation of FaDu carcinoma cells at submicromolar concentrations. Uptake of 3H-TPP by FaDu cells was partially inhibited in medium containing high K+ and fully inhibited by valinomycin in this medium, indicating that TPP accumulates preferentially in mitochondria, and to a lesser extent in the cytoplasm. FaDu cells exposed to TPP exhibited damage to mitochondrial inner membranes, reduced ATP/ADP ratios, decreased oxygen uptake rates and decreased mitochondrial membrane potentials. The treated cells secreted lactate more rapidly than untreated controls and exhibited hypersensitivity to 2-deoxyglucose, an inhibitor of glycolysis. TPP's antimitochondrial effects apparently enhance cytoplasmic glycolysis. In conclusion, TPP inhibits FaDu carcinoma cell growth by inhibiting mitochondrial respiration and ATP synthesis. Cationic phosphonium salts that inhibit carcinoma cell growth through antimitochondrial effects might be used to treat solid tumors without the risk of secondary tumors associated with agents affecting nuclear DNA.

Animals↗

Cationic drug analysis using matrix-assisted laser desorption/ionization mass spectrometry: application to influx kinetics, multidrug resistance, and intracellular chemical change.

Highly sensitive and convenient analysis of intracellular cationic drugs has been achieved by applying matrix-assisted laser desorption/ionization mass spectrometry (MALD-MS). Tetraphenylphosphonium cation was readily identified and quantified (using methyltriphenylphosphonium cation as an internal standard) at subpicomole levels in crude lysate from < 4 x 10(3) FaDu human hypopharyngeal carcinoma cells. A quantitative MALD-MS time course for tetraphenylphosphonium cation accumulation into FaDu cells was comparable to a time course using scintillation counting with tritiated tetraphenylphosphonium. MALD-MS was also capable of demonstrating the reduced accumulation of the cationic drug rhodamine-123 by DoxR MCF7, a multiply drug-resistant human breast adenocarcinoma cell line, relative to the nonresistant parent line MCF7. In addition, MALD-MS was used to follow a chemical reaction inside intact FaDu cells: the formation of a hydrazone (II-51) from benzaldehyde and an acylhydrazide, 5-[tris(4-dimethylaminophenyl)phosphonio]pentanoyl hydrazide (II-25). These results suggest that MALD-MS may provide a rapid and practical alternative to existing methods for the analysis of cationic drugs, toxins, and their metabolites in cells and tissues.

Adenocarcinoma↗

Electromyographic feedback in the treatment of bilateral facial paralysis: a case study.

Electromyographic feedback in the treatment of facial paralysis has been shown to be a useful alternative to surgical procedures. In this paper we report on the partial recovery of a 7-year-old patient with congenital bilateral facial paralysis (Moebius syndrome) that had been considered untreatable by medical specialists. Biofeedback of electromyographic activity was provided together with specific instructions, social reinforcement, and exercises that the patient carried out at home. The rehabilitation training lasted 1 year, during which there was a substantial increase in the electromyographic activity of the muscles on both sides of the face. A follow-up after 1 year of discontinuing the treatment showed that the muscle activity had been maintained and that there was a marked improvement in the patient's mood and facial expression.

Abducens Nerve↗

[The significance of meconium in the intrahepatic cholestasis of pregnancy].

1. We studied 202 pregnant women who were porter of pregnancy intrahepatic cholestasis (CIE). They were attended at the High Risk Fetus Unity (FAR) at the Hospital Salvador Maternity. They were compared with a control group that was composed by 404 patients with normal pregnancy. 2. The patients with CIE presented three times more risk of having a newborn infant of preterm than the other group (p < 0.01) omitting the cesarean factor. 3. The patients with CIE but without an associated pathology, also didn't present a greater risk of having a newborn infant of below weight (< 2,500 g) neither a newborn infant with Apgar 1' > 7, at any gestational age and any way of delivery, than the control group. 4. The risk of having meconium is three times greater in the patients with CIE. This risk increases (Odds ratio = 4.87 with p < 0.01) when they present an associated pathology. 5. Analyzing separately the group of patients with CIE and meconium and comparing with the control group, we didn't find any difference between both groups in relation with the risk of below weight (< 2,500 g), Apgar 1' < 7 and strangely preterm delivery. 6. The presence of meconium in patients with CIE and without an associated pathology, disposing adequate monitoring of pregnancy and delivery, is postulate that it isn't in relation with bad new born infant prognostic.

Case-Control Studies↗

The HLA system and T-cell subsets in Bell's palsy.

The etiology of Bell's palsy (BP) is still unknown, but infectious, immunological and genetic factors have been suggested to play a role in the pathogenesis of the disease. We analyzed blood samples of 92 Mexican Mestizo patients diagnosed as having BP according to established international criteria, and the results were compared to a group of apparently healthy controls of the same ethnic origin. HLA class I (A, B, C) and Class II (DR, DQ) products of the major histocompatibility complex (MHC), and the percentages of CD3, CD4 and CD8 T-cell subsets were investigated. The number of family antecedents was surprisingly high (46%), supporting a genetic basis. There was a slight increase of DRw13, suggesting a possible susceptibility class II-linked gene. A significant decrease of DR4 (pc = 0.001) was detected, which may indicate the existence of a resistance DR-linked gene. Thus, a non DR4 carrier may be in high risk of expressing BP. In the acute phase of the disease, the T-cell subsets showed a decrease in CD3 and CD4 cells when compared to controls. CD8 cells were increased in the same stage. A transient T-cell imbalance was thus observed which recovered in the convalescent phase. None of the patients with CD4 lower than 40% were DR4, suggesting that the DR-linked resistance gene may predispose to the T-cell defect.

Adult↗